The 3D pharmacophore modeling to explore new antischistosomal agents among US FDA approved drugs.

Aim: To identify potential antischistosomal agents through 3D pharmacophore-based virtual screening of US FDA approved drugs. Materials & methods: A comprehensive virtual screening was conducted on a dataset of 10,000 FDA approved drugs, employing praziquantel as a template. Promising candidates were selected and assessed for their impact on Schistosoma mansoni viability in vitro and in vivo using S. mansoni infected mice. Results & conclusion: Among the selected drugs, betamethasone and doxazosin demonstrated in vitro efficacy, with effective concentration 50% (EC50) values ranging from 35 to 60 µM. In vivo studies revealed significant (>50%) reductions in worm burden for both drugs. These findings suggest that betamethasone and doxazosin hold promise for repurposing in treating schistosomiasis. Additionally, the study showcases a useful approach for identifying new antischistosomal drugs.

Discovering new treatments for #schistosomiasis is crucial[Formula: see text]. Our study used virtual screening to identify potential antischistosomal drugs from US FDA approved compounds [Formula: see text]. Promising results in vitro and in vivo. [Formula: see text] #drugdiscovery #tropicaldiseases.

Evaluating the Antischistosomal Activity of Dehydrodieugenol B and Its Methyl Ether Isolated from Nectandra leucantha-A Preclinical Study against Schistosoma mansoni Infection.

Schistosomiasis, a parasitic disease affecting nearly 250 million individuals globally, poses a significant health challenge. With praziquantel being the sole available treatment and its limited efficacy in early stage infections, the identification of novel bioactive compounds becomes imperative. This study examines the potential of dehydrodieugenol B (1) and its methyl ether (2), derived from the leaves of the Brazilian Nectandra leucantha plant (Lauraceae), in combatting Schistosoma mansoni infections through a preclinical approach. Initially, compound 1 displayed noteworthy in vitro antiparasitic activity with an EC50 of 31.9 µM, showcasing low toxicity in mammalian cells and an in vivo animal model (Caenorhabditis elegans). Conversely, compound 2 exhibited no activity. In silico predictions pointed to favorable oral bioavailability and the absence of PAINS similarities. Subsequently, a single oral dose of 400 mg/kg of compound 1 or praziquantel was administered to mice infected with adult (patent infection) or immature parasites (prepatent infection). Remarkably, in prepatent infections, 1 resulted in a significant reduction (approximately 50%) in both worm and egg burden, while praziquantel reduced worm and egg numbers by 30%. The superior efficacy of dehydrodieugenol B (1) compared to praziquantel in premature infections holds the potential to advance the development of new molecular prototypes for schistosomiasis treatment.